This invention relates to crystalline, low melting, xcex5-caprolactone polymers bearing basic amine functionalities which are linked to the ester chain ionically or covalently to induce catalyzed hydrolysis. The ester components can be derived from xcex5-caprolactone with or without small amounts of glycolide, and/or similar lactones. Such polymers with accelerated absorption profiles are especially adapted for use as transient coatings for absorbable multifilament surgical sutures and other medical implants.
Multifilament surgical sutures such as Dexon(copyright) polyglycolide multifilament suture typically require a surface coating to improve their handling and knotting characteristics. Capitalizing on the desirable low melting temperature, crystallinity, and rheological properties of polycaprolactone and its copolymers as coating materials, several compositions based on this polymer were investigated as coatings for surgical sutures. Recognizing the fact that the xcex5-caprolactone homopolymer is essentially non-absorbable led to the development of copolymers of xcex5-caprolactone with variable amounts of more absorbable monomers to improve the coating absorbability. U.S. Pat. No. 4,624,256 discloses a suture coating copolymer of at least 90 percent xcex5-caprolactone and a biodegradable monomer and optionally a lubricating agent. Examples of monomers for the biodegradable polymers disclosed include glycolic acid and glycolide, as well as well-known monomers typically used to prepare absorbable polymer fibers or coatings for multifilament sutures. U.S. Pat. Nos. 4,788,979 and 4,791,929 disclose a bioabsorbable coating of a copolymer of at least 50 percent xcex5-caprolactone and glycolide. Sutures coated with such polymers are reported to be less stiff than sutures coated with other materials and the physical properties of the coated suture are also reported to be acceptable. U.S. Pat. No. 4,994,074 discloses copolymers of a predominant amount of xcex5-caprolactone, the balance being glycolide and glycolic acid. The use of glycolic acid as a comonomer into the copolymers of this invention was reported to increase the rate of absorption of the copolymer when used as a coating for multifilament surgical sutures.
Unfortunately, the problem of adequate bioabsorbability of xcex5-caprolactone-based polymers without detrimental effects on their desirable properties as coatings still remains. Specifically, the use of sufficient amounts of glycolide to achieve sufficient absorbability of the copolymeric coating can compromise its crystallinity and melting characteristics, for it may become amorphous or liquid near room temperature. On the other hand, the strategy of using glycolic acid to achieve the reported results in coating absorbability does limit the ability to produce sufficiently long chain molecules to achieve optimum frictional properties, due to glycolic acid""s known properties as both a ring-opening initiator or chain terminator. Thus, a totally new approach to modifying the absorbability of polycaprolactone and its copolymers without affecting their desirable properties as suture coatings or coatings for surgical devices would be a more desirable goal.
One aspect of the invention are low melting, crystalline, basic nitrogenous polyesters, or polyesteramides, where the amine functionality represents between 1 and 20 percent of the total weight, while the repeat units of the polyester chain originate predominantly from xcex5-caprolactone. The balance ester sequences can be derived from glycolide, lactide p-dioxanone and/or one or more of the corresponding hydroxy acids. The amine functionality can be linked to the polyester chain ionically or covalently.
In another aspect, the invention is a coating for a surgical suture which displays autocatalyzed hydrolysis and improved absorbability over polyester coatings of the prior art which are devoid of any basic amine functionality. This coating comprises a low viscosity melt or a solution in an organic solvent, of the amine-bearing polyesters described above. Surprisingly, the incorporation of 1 to 10 percent of the amine functionality increased the polyester absorbability substantially, without compromising its desirable physical properties such as those associated with crystallinity and melting profile.
Polyesters bearing the amine-functionalities subject of this invention and coating derived therefrom can be used for coating bioabsorbable multifilament surgical sutures, as well as other surgical closure devices and indwelling devices. In addition, they may be used alone or as carriers or matrices for viable cells and vaccines, or as a coating containing bioactive agents such as growth factors, antimicrobials and antibiotics.
Polyesters comprising predominantly xcex5-caprolactone polymer sequences generally refers to polymers with xcex5-caprolactone-based sequences of greater than 80 mole percent, the monomer compositions from which the polymers of this invention are derived. xcex5-Caprolac-tone is the predominant component of the polyester because of its low melting, exceptionally low glass transition temperature (Tg) and its ability to enhance the surface physical properties of coated multifilament sutures. Preferably, the amount of xcex5-caprolactone used in the synthesis of the polyester ranges from 90 to 99, more preferably 96 to 99 mole percent. For copolyesters of this invention, the remaining comonomers are preferably glycolide and/or glycolic acid. Other lactones such as lactide and p-dioxanone and/or their corresponding hydroxy acids can be used. The hydroxy acids can be used, specifically, as chain initiators to control the polyester molecular weight, as determined in terms of their inherent viscosities (I.V.) as approximately 0.1 g/dl solutions in chloroform, and/or to provide chains with a carboxylic end group. The basic nitrogenous polyesters which are the subject of this invention, are to have I.V. of 0.05 to 0.35 dl/g and, preferably, 0.05 to 0.25 and, more preferably 0.10 to 0.20 dl/g.
Two major types of amine functionalities can be introduced into the polyester chain to accelerate its absorption through autocatalyzed hydrolysis. Excluded from the amine-bearing functionalities are bio-active polypeptides. The weight percent of the amine functionalities in the polyesters subject of this invention can be between 1 and 20 and, preferably, 1 to 10. The first type of amine functionality comprises an ionically linked mono- or poly-functional amine which is capable of forming a carboxylate salt with an acid-terminated polyester chain. This can entail, for instance, a caprolactone/glycolide copolymer made using catalytic amounts of stannous octoate and glycolic acid as the chain initiator, and following a typical reaction scheme established for caprolactone polymerization. The resulting acid terminated polyester is then allowed to form carboxylate salts with amine-bearing molecules: lysine, l-lysine, potassium lysinate, or an alkane diamine as depicted by structures A and B, respectively. 
The second type of amine functionality is covalently incorporated into the polyester chain. This can be achieved by amidation of preformed polyester with di- or poly-functional amine or using di- or poly-amine with at least one reactive hydrogen as the chain initiator, such as 1-methyl 4-aminomethyl-piperidine and 3,3xe2x80x2-diamino-N-methyl-diproppylamine. The ring opening polymerization can be achieved using catalytic amounts of stannous octoate. Typical polyesters covalently linked to the amine functionalities can be illustrated by structures D and E shown below. 
Although this invention addresses low melting crystalline polyesters made predominantly of xcex5-caprolactone, those skilled in the art can foresee the use of other aliphatic polyesters as the base materials and incorporate the amine functionality to the aid terminated polyester chains by salt formation or the amidation of pre-formed polyester chains using amino compounds similar to those associated with structures D and E above.
The coating can be applied to the braided suture as a low viscosity melt at temperatures between 70xc2x0 C. and 100xc2x0 C. and, preferably 70xc2x0 C. and 90xc2x0 C. Excess coating can be removed by passing through a pad of non-woven fabric, e.g., polypropylene or a sizing die. More traditional methods of coating application can entail the use of 1 to 15 percent solution and, preferably, 2 to 10 percent in an organic solvent such as toluene at room temperature or between 25xc2x0 C. and 50xc2x0 C. The solvent can then be evaporated by air-drying at room temperature or between 25xc2x0 C. and 75xc2x0 C. Other solvents or mixture of solvents can be used as substitutes for toluene or acetone. The coated suture can be further treated thermally to insure even distribution of the coating on the braid components. Typical sutures which can be coated with compositions subject of this invention include those made of polyglycolide and polyethylene terephthalate. Depending on the suture size, the percent add-on of the coating can be varied between 1 and 10 percent and, preferably, 1.5 to 4.5 percent as the suture decreases from say size #1 to size #6-0. At such level of coating, the suture handling and tie-down characteristics are improved substantially without compromising other properties such as visibility, surface appearance, and knot strength and security.
The absorption profile of the coating is such that it will not affect that of an absorbable suture to any discernable extent, Typically, when representative coatings subject of this invention are used on polyethylene terephthalate sutures incubated in a phosphate buffer at 37xc2x0 C. and pH of 7.26 lose 50 to 100 percent of their original mass in two to six months.